SPARC (secreted protein acidic and rich in cysteine), also known as osteonectin and BM-40, is an extracellular matrix (ECM)-associated glycoprotein widely distributed in human and murine tissues undergoing developmental regulation. While its specific role remains elusive, the high degree of interspecies conservation suggests a strong evolutionary pressure to conserve this protein. Extensive studies thus far have implicated SPARC in diverse functions including cell proliferation [Lane and Sage, FASEB J., 8:163-173 (1994)].
ECM proteins are required for growth factor stimulated cell proliferation since anchorage dependent cells grown as suspension cultures in the absence of ECM die eventually. However, the role of individual ECM proteins to support the growth induced by individual growth factor is not known. SPARC has been shown to influence cell growth in a cell type-specific manner. Down-regulation of SPARC did not perturb melanoma cell growth, while over-expression in ovary cancer cell lines or addition of purified SPARC to endothelial cells retarded cell growth [Ledda et al, Nature Med., 3:171-176, (1997); Mok et al., Oncogene, 12:1895-1901 (1996); Funk and Sage, J. Cell. Phsiol., 154:53-63 (1993)]. Nevertheless, peptides corresponding to SPARC domain II stimulate cell proliferation [Funk and Sage, J. Cell. Physiol., 154:53-63 (1993)]. This result strongly suggests that extracellular cleavage may have important consequences on the ability of SPARC to modulate cell growth. Furthermore, SPARC was shown to interact with growth factors, cytokines and ECM components [Lane and Sage, FASEB J., 8:163-173 (1994)], indicating that SPARC may profoundly influence cell growth through these diverse functions.
The role of SPARC in cell proliferation is further supported by its expression in sprouting endothelial cells and endothelial cords during angiogenesis and in fibroblasts and macrophages migrating into wound sites [Sage and Bornstein, J. Biol. Chem., 266:14831-14834 (1991); Reed et al., J. Histochem. Cytochem., 41:1467-1477 (1993)]. Moreover, SPARC is highly expressed in actively dividing osteoblasts, hypertrophic chondrocytes at growth plates and in developing embryos [Lane and Sage, cited above].
SPARC is abundantly expressed in extraembryonic parietal endoderm [Mason et al, EMBO J., 5:1465 (1986)], which specializes in the synthesis and secretion of a thick basement membrane known as Reichert's membrane or the parietal yolk sac. This membrane acts as a barrier keeping embryonic fluid inside to provide nutrients to embryos and to protect embryos from outside shock. SPARC is expressed in the heart, lung and somites of embryos. Somites differentiate into vertebrae, ribs, muscles and dermis of skin. Transgenic nematodes over-expressing SPARC are abnormal. Embryos are deformed, and adults show reduced mobility and paralysis, suggesting the involvement of SPARC in the adhesion of muscle cells to the ECM [Schwarzbauer and Spencer, Mol. Biol. Chem., 4:941-952 (1993)]. Microinjection of SPARC antibodies into Xenopus embryos resulted in abnormal axial development and developmental arrest at the neurula and tailbud stages [Purcell et al., J. Exp. Zool., 265:153-164 (1993)].
There is a need in the art, especially in the medical and pharmaceutical fields, for commercial research and diagnostic systems useful for testing cell proliferation and screening for diseases resulting from impaired cell proliferative processes.